In this assessment of the effect of manidipine hydrochloride (CV-4093(2HCl)) on late in utero development, parturition, lactation, and subsequent development and fertility and reproductive performance of the F1 generation, dosages of 1, 3 and 10 mg/kg/day were administered by oral intubation to dams from day 15 of gestation to day 21 of lactation. All females were allowed to deliver and rear their young. Because of equivocal results in F1 fertility in the main study and failure to confirm or deny these results, a supplemental study was initiated. This report combines the presentation of the methods and results of both studies. Lower body weight gain values and/or food consumption were observed in the F0 animals of the high-dose group in the main and supplemental studies. Prolonged or difficult delivery was observed in the F0 females of the same group in both studies. This resulted in the death or sacrifice of at least one animal per study. The mean duration of gestation was significantly longer in F0 females of the high-dose group compared to the control group. The number of F1 stillborn pups, missing, or cannibalized pups and overall neonatal pup deaths was higher in the high-dose group than the control group. Growth, body weights, morphologic findings, physical development (pinna unfolding, incisor eruption, eye opening, testes descent, and vaginal opening) of the F1 pups and weaning index were unaffected by treatment of the F0 females. Functional development (negative geotaxis, tail flick, pupillary reflex, and auditory response) and behavior (open field testing and water T-maze testing) of the F1 animals were also similar in all groups. There were equivocal results in fertility of F1 animals in the main study; the pregnancy rates were 90%, 89%, 78% and 65% at 0, 1, 3 and 10 mg/kg/day, respectively. Rebreeding to confirm or deny the effect on fertility was not possible because the animals served as alternates for evaluation of F1 breeding were sacrificed. In the supplemental study, no effect on fertility was observed in any group; the pregnancy rate was 100% for all groups. Therefore, an effect on fertility of F1 animals in the main study is not considered to be a treatment-related effect. It may have been reflect that vaginal lavage technique was performed to confirm the matimg in the main study but not in the supplemental study, and females were separated if mating was detected in the main study but not in the supplemental study. F2 pup viability was below the control level in the high-dose group in the supplemental study. However, this was not considered to be a treatment-related effect since it was evident only in the supplemental study. From these results of the main and supplemental studies, it was concluded that the no-effect dosage level for dams and pups was 3 mg/kg/day under these experimental conditions.